Previously, we have investigated the mechanism of action of interferons (IFNs). In our present research we are focusing on the biochemical studies of interleukin-6 (IL-6). We have identified two IL-6 binding proteins with apparent Mr of 80 and 108 kDa. These two proteins which appear to have different affinities for IL-6 can be visualized as an 100 and a 130 kDa receptor complex upon affinity-crosslinking with iodinated recombinant IL-6. Our studies indicate that the IL-6 binding protein contained within the 130 kDa complex comprises a novel, high-affinity IL-6 receptor which has not been described previously. We observed that the expression of both IL-6 receptor molecules varies with cell lineage. In addition, we have demonstrated that the 108 kDa receptor mediates the internalization of its ligand. These findings are important for the elucidation of the signalling pathway of IL-6, which is currently poorly understood. We also investigated whether IFN could modulate the expression of the IL-6 receptors, and our data indicate that IFN down-regulates the IL-6 receptors. Since IFN causes growth arrest of human myeloma cell lines which express both IL-6 receptors, we will test the notion whether the antiproliferative mode of action of IFN in myeloma cell lines is due to the disruption of a functional IL-6 receptor-signalling pathway. Our main research effort, however, will focus on the biochemical and molecular elucidation of the structure and function of the 108 kDa IL-6 receptor. Purification and molecular cloning of the receptor are in progress.